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Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation, and Metabolism
- Source :
- Cell metabolism. 24(6)
- Publication Year :
- 2016
-
Abstract
- Adipocytes package incoming fatty acids into triglycerides and other glycerolipids, with only a fraction spilling into a parallel biosynthetic pathway that produces sphingolipids. Herein, we demonstrate that subcutaneous adipose tissue of type 2 diabetics contains considerably more sphingolipids than non-diabetic, BMI-matched counterparts. Whole-body and adipose tissue-specific inhibition/deletion of serine palmitoyltransferase (Sptlc), the first enzyme in the sphingolipid biosynthesis cascade, in mice markedly altered adipose morphology and metabolism, particularly in subcutaneous adipose tissue. The reduction in adipose sphingolipids increased brown and beige/brite adipocyte numbers, mitochondrial activity, and insulin sensitivity. The manipulation also increased numbers of anti-inflammatory M2 macrophages in the adipose bed and induced secretion of insulin-sensitizing adipokines. By comparison, deletion of serine palmitoyltransferase from macrophages had no discernible effects on metabolic homeostasis or adipose function. These data indicate that newly synthesized adipocyte sphingolipids are nutrient signals that drive changes in the adipose phenotype to influence whole-body energy expenditure and nutrient metabolism.
- Subjects :
- 0301 basic medicine
FGF21
Physiology
Serine C-Palmitoyltransferase
Adipose tissue
White adipose tissue
Body Mass Index
chemistry.chemical_compound
Mice
0302 clinical medicine
Adipose Tissue, Brown
Adipocyte
Adipocytes
Cell Differentiation
Thermogenesis
Adrenergic beta-Agonists
Middle Aged
Cold Temperature
Organ Specificity
030220 oncology & carcinogenesis
Adult
medicine.medical_specialty
Adipose tissue macrophages
Subcutaneous Fat
Adipokine
Dioxoles
Carbohydrate metabolism
Biology
Ceramides
03 medical and health sciences
Young Adult
Internal medicine
medicine
Diabetes Mellitus
Animals
Humans
Obesity
Molecular Biology
Aged
Inflammation
Sphingolipids
3T3-L1
Cell Biology
Fatty Liver
030104 developmental biology
Endocrinology
Glucose
chemistry
Gene Expression Regulation
Energy Metabolism
Gene Deletion
Subjects
Details
- ISSN :
- 19327420
- Volume :
- 24
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Cell metabolism
- Accession number :
- edsair.doi.dedup.....387a97be7d1a4c6ed06f2462fd42b761